tbuckley/cabot-search huggingface dataset:
Abstract 13614: Why the Pulmonary Veins: Linking Atrial 4D Flow MRI Derived Biomechanics and Pulmonary Vein Electrical Remodeling
Authors: Andrew C Nickel, Cody J Johnson, Brandon A Tran, Blake E Fleeman, Ryan T Kipp, Daniel S Modaff, Jennifer M Wright, Alexey V Glukhov, Alejandro Roldan Alzate, Matthew M Kalscheur
Journal: Circulation (2022)

Introduction: Pulmonary veins (PV) often trigger atrial fibrillation (AF). However, the underlying mechanism is not completely understood and predicting who benefits from PV isolation (PVI) is imprecise. We propose that arrhythmogenic PV remodeling may be related to myocardial mechanical function. Flow-encoded cardiac magnetic resonance imaging (4D Flow MRI) based computational modeling enables assessment of left atrial (LA) hemodynamics and biomechanics. In this pilot study, 4D Flow MRI derived parameters were compared to invasive electroanatomic mapping (EAM) and hemodynamics to explore potential non-invasive evaluation of PV remodeling and arrhythmogenicity. Methods: Patients (5 female, 4 male, age 64±6.7 years) with paroxysmal or early persistent AF scheduled for PVI were enrolled. All patients underwent 4D Flow MRI prior to ablation (in sinus rhythm) and intraprocedural EAM (Carto) with atrial pacing under baseline conditions and after increasing LA pressure with a fluid bolus. Non-invasive measures included peak and average velocity (m/s) and net flow (ml/cycle) in each vein (n=36) and averaged for each patient. Apparent conduction velocities in the proximal, mid and distal portions of each vein were calculated under baseline and stretch conditions from EAM. Change in LA pressure per volume bolus, a measure of atrial stiffness, was compared to non-invasive parameters. Results: In patients with LA stiffness greater than median, peak velocities (0.77±0.12 vs. 0.62±0.24 m/s, p=0.26) and net flows were higher (17±2.0 vs. 14.0±2.4 ml/cycle, p=0.06). Patients with paroxysms of spontaneous arrhythmias during mapping had higher LA stiffness (11.5±5.7 vs. 7.6±5.3 mmHg/L, p=0.30). There was a significant correlation between non-invasive average velocity and apparent conduction velocity in the proximal portion of the vein (R=-0.36, p=0.03) and the suggestion of a correlation between increasing peak flow velocity and decreased apparent conduction velocity under stretch conditions compared to baseline (R=-0.24, p=0.16). Conclusions: Our findings may indicate a link between atrial hemodynamics, electrical remodeling and PV arrhythmogenicity. Additional studies are warranted to confirm and better define these findings.
Abstract 13595: <i>Lactobacillus</i> Supplementation Augments Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
Authors: Sasha Z Prisco, Anna Park, Rashmi Raveendran, Kurt W Prins
Journal: Circulation (2022)

Introduction: Gut microbiome dysbiosis induces hyperactivation of the immune systemic in multiple diseases. In pulmonary arterial hypertension (PAH), dysbiosis could therefore regulate right ventricular (RV) function because inflammatory glycoprotein 130 (GP130) signaling pathologically restructures RV microtubules and junctophilin-2 (JPH2) to promote RV dysfunction (RVD) in MCT rats. Interestingly, increases in intestinal Lactobacillus, an anti-inflammatory bacteria, by intermittent fasting enhance RV function in monocrotaline (MCT) rats. However, it is unknown if Lactobacillus supplementation can restructure the microbiome to suppress GP130-mediated RVD. Methods: Male rats were randomly allocated into 3 groups: control, MCT water gavage (MCT-water), and MCT Lactobacillus rhamnosus (4x10 7 CFU/day) gavage (MCT- Lactobacillus ) with treatments starting 2 weeks after MCT injection. Next-generation sequencing evaluated the composition of the bacterial and fungal components of the microbiome. SomaScan proteomics quantified levels of serum GP130 ligands. Immunoblots probed RV microtubule and JPH2 expression. Echocardiography and closed-chest pressure-volume (PV) loops determined RV function. Results: Lactobacillus supplementation restructured the micro/mycobiome, and concomitantly improved jejunal epithelial cell morphology. Serum proteomics revealed Lactobacillus treatment decreased circulating GP130 ligand levels which normalized RV microtubule and JPH2 protein expression. Finally, Lactobacillus reduced RV hypertrophy and fibrosis and enhanced RV function without changing PAH severity. Conclusions: Lactobacillus supplementation restructured the microbiome, dampened GP130 activation, normalized RV microtubule and JPH2 expression, and augmented RV function. Thus, Lactobacillus treatment could be a readily translatable approach to combat RVD in PAH.
Abstract 13553: Remote Monitoring of the Haemodynamic Response to Clinically Indicated Therapeutic Escalation and Clinical Worsening Events in Patients With Pulmonary Arterial Hypertension
Authors: Jennifer T Middleton, Sarah Binmahfooz, Hamza Zafar, Junaid Patel, Dharshan Giri, Christian Battersby, Mark Toshner, Ashwin Reddy, Robert Lewis, Robin Condliffe, Charlie Elliot, Abdul Hameed, Athanasios Charalampopoulos, Alfred Thompson, David G Kiely, Alex M Rothman
Journal: Circulation (2022)

Background Hospital-based assessment of haemodynamics, exercise capacity and right heart function/strain are used for risk-stratification to aid clinical decision making and guide treatment in patients with pulmonary arterial hypertension. Advances in haemodynamic and cardiac monitoring now provide the capacity to remotely measure physiological parameters that relate to mortality from a patient’s home. We sought to examine remote monitored physiology in the time preceding and following increase in standard of care therapy and clinical worsening events in patients with pulmonary arterial hypertension. Methods Between January 2020 and October 2021 22 patients with WHO functional class III PAH and a hospitalisation in the preceding year were implanted with a pulmonary artery pressure monitor (CardioMEMS, Abbott) and an insertable cardiac monitor (LinQ, Medtronic) (FITPH 19/YH/0354). Remote data and clinical events were reviewed in a multidisciplinary team identifying 18 increases in therapy and 13 worsening events. For each parameter baseline was set at the 30-days preceding the event and daily data analysed as change from baseline. Statistical significance was determined using Wilcoxon matched pairs and One-way ANOVA with Dunnett’s correction as appropriate. Results Following clinically indicated increase in therapy improvements in field walk test, WHO functional class and NT-proBNP were observed (p&lt;0.05) with mean time to follow up of 5.1 months. Remote monitored mean pulmonary artery pressure and total pulmonary resistance were reduced and cardiac output and physical activity increased compared to baseline at day 7, 4, 22 and 42 respectively (p&lt;0.05). Clinical worsening events led to deterioration in field walk test, WHO functional class and NT-proBNP (p&lt;0.05). Remote monitored mean pulmonary artery pressure and total pulmonary resistance were increased and cardiac output and physical activity reduced 10 days prior to a clinical worsening event (p&lt;0.05). Conclusion Remote haemodynamic and cardiac monitoring may provide a means for early, remote evaluation of clinical efficacy and early identification of clinical worsening in patients with pulmonary arterial hypertension.
Abstract 14058: Racial Bias in Pulse Oximetric in Pediatric COVID Patients
Authors: Fabio Savorgnan, Sebastian Acosta, Nirica Borges
Journal: Circulation (2022)

INTRODUCTION Pulse oximetric (Sp02) may overestimate patient oxygen saturation. This bias is possible more pronounced in patients of black ethnicity. The current study aimed to assess whether SpO2 accurately predicted laboratory oxygen saturation (SaO2) in symptomatic hospitalized pediatric patients with covid 10. And whether disparities between black and white race ethnicity existed. Methods: This retrospective study evaluates covid 19 patients between May 2020 and December 2021 admitted to Texas Children's Hospital (TCH). We used multivariate logistic regression to examine the association between race and bias in Sp02. The bias is defined as the difference in SaO2 and SpO2. All analyses were performed using Python Statsmodels v0.12.2. Results: There were 4300 patients with covid with complete physiological data in the Sickbay and electronic chart system. Figure 1 shows a paired SpO2 and SaO2 comparison between the white and black hospitalized pediatric patients with covid 19. Figure 2 depicts the paired bias comparison between the black and white hospitalized pediatric patients with covid 19. Multivariate logistic regression showed that the black race-ethnicity is associated with worse bias (OR (95%CI) = -1.94 (-3.22, - 0.65), p&lt;0.003) in the non-invasive oxygen saturation. Discussion: We found a bias in the measurement of Sp02 about Sa02 in symptomatic hospitalized pediatric patients with the diagnosis of covid 19; furthermore, the race-ethnicity is related to an increased bias in the reading of Sp02 about Sa02. Like the previous studies, we consistently found more bias in reading Sp02 about Sa02 in the black population.
Abstract 14102: The Joint Effect of Arterial Stiffness and High Central Blood Pressure on Risk of Stroke Among Hypertensive Adults
Authors: Tianyu Cao, Congcong Ding, Xiao Huang
Journal: Circulation (2022)

Introduction: The increases in arterial stiffness and central blood pressure (cBP) suggest significant status of vascular damages with different physio-pathological progress. However, the joint effect of them on risk of first stroke have remained uncertain. And the predictive value of CAP over peripheral blood pressure (bBP) is controversial. Hypothesis: This study aims to test the hypothesis that the combination of elevated arterial stiffness and central systolic blood pressure (cSBP) can predict first stroke and is associated with highest risks among hypertensive adults. Methods: A total of 7531 hypertensive adults without prior history of stroke were analyzed. cSBP was measured noninvasively using A-Pulse CASPro device. Arterial stiffness was measured by carotid-femoral pulse wave velocity using the noninvasive PulsePen device (WPP001-ET, DiaTecne s.r.l). Whole data was collected from July 2016 to December 2019. Increased arterial stiffness was defined as cfPWV ≥10 m/s. The primary outcome was first all-cause stroke. Results: Of the 7531 participants, mean age was 61.3 ± 9.3 years, 37.2% were male, the mean brachial blood pressure is the mean cfPWV was 9.4 ± 2.2 m/s, the mean cSBP is 131.3 ± 12.8 mmHg. During a mean follow-up time of 3.3 years, 432 (5.2%) participants developed stroke, of which 380 were ischemic strokes. Compared with the reference group (low cfPWV and cSBP), only the group with both high cfPWV and cSBP was significantly associated with risk of stroke after adjusted for covariates (HR: 1.51, 95% CI 1.10, 2.07). Similar result was found in Kaplan Meier Curve. Such association appears robust in different sub-group analysis. Conclusion: The combination of higher arterial stiffness and central systolic blood pressure is associated with highest risk of first stroke compared to other groups. The combined control of arterial stiffness and central blood pressure serves the purpose of primary prevention of first all-cause stroke among hypertensive population.
Abstract 14878: Natural Language Processing of Unstructured Medical Record Can Predict Cardiac Arrhythmia by Quantifying Chronic Disease Burden
Authors: Andy Huang, George Liu, Paul C Lee
Journal: Circulation (2022)

Introduction: Prediction of atrial fibrillation (AF) and sick sinus syndrome (SSS) is difficult. CMS Hierarchical Condition Categories scores (CMS-HCC) is a risk adjustment score used by CMS to account to risk adjust quality and cost metrics by quantifying the burden of chronic disease and patient complexity. Its calculation is based on patient’s demographics and ICD10 diagnostic codes. We have created an algorithm (MYTH) that can determine ICD10 diagnostic codes from unstructured medical chart using Natural Language Processing through syntax analysis, knowledge graph and regular expressions. The ICD-10 codes can then be used to calculate CMS-HCC. Because chronic disease burden may increase the probability of cardiac arrhythmia, we hypothesize that CMS-HCC can predict the onset of atrial fibrillation and sick sinus syndrome. Methods: We used MYTH to automate ICD10 coding and HCC score calculation based on textual outpatient cardiology records of 926 patients. The algorithm was additionally applied to calculate CHA2DS2-VASc scores. These were applied to predict the diagnosis of AF and SSS on clinical follow-up retrospectively. Results: CMS-HCC scores outperforms CHA2DS2-VASc scores in the prediction of onset of AF: (AUC: CHA2DS2-VASc 0.703, CMS-HCC 0.778, difference P=0.0006, individually P&lt;0.0001). While HCC score is predictive of the onset of SSS (P&lt;0.001), its improvement over CHA2DS2-VASc score does not reach statistical significance (AUC: CHA2DS2-VASc 0.702; CMS-HCC 0.744, difference: P=0.297, individually P&lt;0.001). Conclusions: Natural Language Processing algorithms can understand unstructured medical text, automate ICD coding and automate CMS-HCC score calculation. The burden of chronic diseases, as reflected by the CMS-HCC score, is highly predictive of future atrial fibrillation and modestly predictive of sick sinus syndrome.
Abstract 13725: The Dose Difference of Carvedilol for Heart Failure Management Between Asian-Americans and Japanese Could Show No Difference in the Improvement of Heart Function
Authors: Makiko Maeda, Douglas Humber, Eisuke Hida, Tomohito Ohtani, Guannan Wang, Tong Wu, Jun Hayashi, Jacinta N Situ, Shiori Takeda, Hiroshi Okamoto, Toshihiro Takeda, Masatsugu Hori, Yasushi Sakata, Yasushi Fujio, Shirley Tsunoda
Journal: Circulation (2022)

Introduction: Carvedilol has improved cardiac mortality and morbidity for heart failure with reduced ejection fraction (HFrEF). The initial and target doses used in the Japanese randomized controlled trials (RCTs) were almost half of those in the USA leading to markedly lower recommended doses for HF management the in Japanese national guidelines compared to the USA. Hypothesis: Race may play a role in the optimal dose of carvedilol for HFrEF management. Methods: The international collaborative study was performed to compare the dose difference and the effect on heart functions, such as left ventricular EF (LVEF) and heart rate (HR), among Asian-Americans (AA), Caucasians (CA), and Japanese (JA) using real-world data. Each local ethics committee approved the study protocol at the University of California, San Diego (UCSD), the Osaka University Hospital (OUH), and the OU pharmaceutical sciences. The initial population at UCSD Health and OUH consisted of 1078 patients with HFrEF (≥ 20 years, EF&lt;40%) treated with carvedilol (668 AA and CA and 410 JA). After inclusion/exclusion criteria, the study population consisted of 26 AA, 36 CA, and 96 JA. Results: Initial carvedilol dose (mg/day) (AA, 14.5 ± 11.9; CA, 19.1 ± 18.7; JA, 4.3 ± 4.2) and the dose at one year (30.9 ± 22.4; 34.5 ± 21.4; 11.2 ± 6.5) were significantly lower for JA compared to AA or CA ( p &lt; 0.05 vs JA, respectively). AA had the highest frequency of carvedilol discontinuation (%; AA, 10.7; CA, 2.6; JA, 6.5) and dose reduction (18.4, 10.7, 2.2) ( p &lt; 0.05, chi-square test). Clinical measurements of LVEF (%) measured before carvedilol initiation and after one year (before; 28.9 ± 8.8, 26.5 ± 8.0, 28.8 ± 7.4, after; 42.9 ± 11.1, 37.5 ± 15.3, 41.2 ± 13.1) and HR (beats/min) (before; 81.9 ± 19.0, 77.7 ± 13.5, 74.7 ± 10.9, after; 77.8 ± 10.6, 74.0 ± 12.5, 69.4 ± 9.4) showed no significant difference among the three groups. There were also no significant differences in event-free survival and in changes from baseline to 1 year in LVEF and HR, LVDd, or LVDs. Conclusions: JA patients exhibited similar effectiveness compared to AA and CA despite markedly lower carvedilol doses. Doses in AA were more similar to CA vs JA. Dose-deescalation may be an option in Asian HFrEF patients intolerable to high doses of carvedilol.
Abstract 14238: Coronary Artery Calcium for Stroke Mortality Prediction: The Coronary Artery Calcium Consortium
Authors: John Erhabor, Ellen Boakye, Zeina A Dardari, Albert D Osei, Olufunmilayo Obisesan, Kunal Jha, Sant J Kumar, Alan Rosanski, Daniel Berman, Matthew Budoff, Michael D Miedema, Michelle C Johansen, Khurram Nasir, John A Rumberger, Leslee J Shaw, Michael J Blaha
Journal: Circulation (2022)

Introduction: Coronary artery calcification (CAC) is a noninvasive biomarker of atherosclerotic plaque burden in the general population and predicts coronary heart disease and mortality. This study examined whether CAC predicts stroke mortality independent of established traditional cardiovascular risk factors. Methods: We included 66,511 participants (mean age: 54.4±10.6 years; 33.0% women) from the prospective, multi-center CAC Consortium study without stroke or coronary heart disease (CHD). CAC was assessed at the study baseline with a cardiac-gated computed tomography scan and categorized as absent/present and 0, 1-99, 100-299, and ≥300 Agatston Units (AU). To examine CAC as a predictor for stroke mortality, we utilized multivariable-adjusted Fine and Gray competing risk regression models, adjusting for traditional cardiovascular risk factors. For sensitivity analysis, we excluded patients whose death certificates indicated a possible stroke-complication of CHD (excluded, n=8). Results: During a mean follow-up period of 12.3±3.9 years, there were 160 stroke deaths. Compared to individuals without CAC, those with CAC &gt;0 AU had a higher incidence of stroke mortality (0.31 vs. 0.06 per 1,000 person-years). After adjusting for traditional risk factors, individuals with CAC had a significantly higher sub-distribution hazard ratio (SHR) for stroke mortality than those without CAC (SHR: 2.17; [95% CI:1.32-3.56). In addition, compared with individuals without CAC, the risk of stroke mortality significantly increased as CAC increased (SHR range:1.77; [95%CI: 1.03-3.05]) - 3.09; [95% CI:1.72-5.54]). The results obtained from our sensitivity analysis were similar (Table). Conclusions: CAC was associated with mortality from stroke independent of traditional cardiovascular risk factors. While a marker of coronary atherosclerosis burden, CAC should be considered a risk marker for all types of atherosclerotic cardiovascular disease mortality.
Abstract 13646: APOL1 Nephropathy Risk Variant Alters Macrophage Metabolism
Authors: Matthew Wright, Esther Liu, Valerie Garcia, Jennie Lin
Journal: Circulation (2022)

The common G1 and G2 variants in the APOL1 gene, specific to patients with African ancestry, increase the risk of developing chronic kidney disease and stroke. These variants also confer a survival benefit against African trypanosomiasis, but the effects of G1 and G2 variants on macrophage function remain unclear despite their role in innate immunity. Crucial to both innate immunity and tissue homeostasis, macrophages can promote cardiometabolic disease if dysregulated. Others have shown that metabolic changes can alter macrophage phenotype and function, and the G1 and G2 variants have been linked to mitochondrial dysfunction in epithelial cells. We therefore hypothesize that APOL1 risk variants promote cardiometabolic disease traits by altering macrophage metabolism and, thus, function. To test our hypothesis, we established CRISPR-Cas9 genome-edited induced pluripotent stem cell (iPSC) lines with the G0/G0 (major allele) genotype and the G1/G1 genotype on isogenic backgrounds. We then differentiated these iPSC lines into macrophage-like cells (iPSDMs) and evaluated their phenotype and function at baseline and under stimulation with 5 - 50 ug/mL interferon-γ, a potent inducer of APOL1 expression. We measured inflammatory markers via QPCR and ELISA, mitochondrial oxygen flux with the Agilent Seahorse XF Analyzer, and intracellular hydrophilic metabolites via LCMS. We found that G1/G1 iPSDMs express higher levels of pro-inflammatory markers and exhibited lower basal respiration as well as lower ATP production compared to G0/G0 controls. Because APOL1 risk variants have been linked to defective autophagy and ER stress, we treated the G1/G1 iPSDMs with rapamycin (autophagy inducer) or TUDCA (ER stress inhibitor) but found that they did not abrogate these genotype-specific differences in metabolic flux. Upon examination of metabolomics profiles of G1/G1 vs G0/G0 iPSDMs, differentially abundant metabolites were enriched for SMPDB pathways including spermidine biosynthesis (needed for anti-inflammatory reprogramming), gluconeogenesis, Warburg effect, homocysteine degradation, and fatty acid oxidation. Taken together, G1/G1 iPSDMs exhibit metabolic differences that may contribute to their proinflammatory phenotype.
Abstract 13527: The Development of a Remote Pulmonary Arterial Hypertension Risk Score Utilising Remote Monitoring Technology to Monitor Parameters Associated With Mortality in Pulmonary Arterial Hypertension
Authors: Jennifer T Middleton, Sarah Binmahfooz, Hamza Zafar, Junaid Patel, Dharshan Giri Neelam Naganathan, Christian Battersby, Mark Toshner, Ashwin Reddy, Robert Lewis, Andrew J Swift, Robin Condliffe, Charlie Elliot, Abdul Hameed, Athanasios Charalampopoulos, Alfred Thompson, David G Kiely, Alex M Rothman
Journal: Circulation (2022)

Background: In patients with pulmonary arterial hypertension (PAH) risk stratification is used to aid clinical decision making and guide treatment categorising patients as low (&lt;5%), intermediate (5-10%), or high mortality risk (&gt;10%) at 1 year based on hospital investigations. Risk stratification based on remote parameters may facilitate early evaluation of clinical efficacy following treatment change or indicate clinical stability/deterioration, thereby permitting early intervention. Methods: Patients with PH were identified from the ASPIRE (6/YH/0352) database 2/2001-6/2019. Random allocation was used to form a derivation (n=3832). Univariate Cox Regression and stepwise forward multivariate analysis were undertaken in the derivation cohort to identify parameters that may be remote monitored that were associated with mortality. Mortality weighted z-scores of age, incremental shuttle walk test (ISWT), heart rate (HR) and total pulmonary resistance (TPR) were summed to give an individual remote risk score value. LOESS regression was used to determine 1 year risk thresholds applied to a PAH validation cohort (n=590). Results: Multivariate analysis of the derivation cohort demonstrated that ISWT, HR and TPR had statistically significant relationships to mortality. Survival analysis showed increased mortality with each decile of baseline risk score with the 10 th decile at increased risk of mortality compared the 1 st decile (OR 5.5, 95%CI 4.3-7.0, each decile p&lt;0.01, Figure). In patients with PAH, LOESS derived thresholds identified patients at low, intermediate and high risk with 1 year mortalities of 4.6, 9.8 and 15.1% respectively (low-int OR 1.9, low-high OR 2.7,p&lt;0.01,Figure). Conclusion: A score of remote monitored parameters, when applied at diagnosis, accurately categorised patients as low, intermediate, or high risk. This system may be applied to remote monitored physiological data to provide real time risk stratification.